Defects of platelet function are associated with abnormal bleeding conditions, including easy bruising, petechiae and purpura and are a common cause of excessive bleeding due to surgery or trauma. Hyper-responsive platelets may predispose to thrombosis, embolism, ischemia and infarction. It is therefore desirable to be able to determine platelet function and to diagnose platelet dysfunction by reliable and convenient in vitro tests, which reflect meaningfully on platelet function in vivo.
Presently available tests of platelet function include tests relating to clotting time, such as Bleeding Time, and tests involving evaluation of platelet response to activating agents such as thrombin, fibrillar collagen and ADP.
None of these tests have proved good predictors of platelet function in vivo. Probably the best available test for predicting abnormal bleeding during surgery is the Bleeding Time, but even this is poorly predictive.
An important trigger for primary platelet activation in vivo is contact with the subendothelial basement membrane exposed due to damage to the endothelial lining of blood vessels or contact with the intima of the vessel wall through more severe injury, or rupture of an atherosclerotic plaque.
Various lines of investigation suggest that cells and platelets may show a response to an immobilised activating agent which is different from the response of the same cell or platelet to that agent in soluble form. (Schwartz et al., (1991) Proc. Natl. Acad. Sci., vol. 88, pp. 7849-7853; Griffith et al., (1991), Blood, col. 78, pp. 1753-1759).
Tests of platelet activation by soluble agonists may, therefore, not reflect the relevant events involved in haemostasis or thrombosis in vivo.
Coller et al., (1989), Blood, vol. 74, p. 182, have examined platelet agglutination in response to immobilised collagen with a view to identifying the molecular receptor for collagen on the platelet surface. They did not, however, examine collagen-induced agglutination in relation to any clinical conditions.
Coller et al., (1980), Blood, vol. 55, p. 169, also examined platelet agglutination in response to immobilised fibrinogen and noted an impaired response in two patients with thrombasthenia, a condition known to be associated with an abnormality of platelet-fibrinogen interaction.
A need remains for a convenient clinical test which will reflect physiologically relevant in vivo function or dysfunction of the platelet.